Anel Azamatova

Purified water is one of the most important technological utilities in pharmaceutical manufacturing and is widely used in the synthesis of pharmaceutical substances, preparation of technological solutions, equipment sanitation, and production processes. The stability of its physicochemical and microbiological characteristics directly affects the quality, safety, and reproducibility of pharmaceutical products. Therefore, qualification and validation of water treatment systems are essential requirements of Good Manufacturing Practice (GMP).

Background: Iodine-based antimicrobial systems remain highly attractive due to their broad-spectrum activity; however, the clinical application of free iodine is limited by its instability and cytotoxicity. This study aimed to develop polyethylene glycol (PEG)-based hydrophilic ointment formulations containing a dextrin/polyvinyl alcohol/iodine complex (D/PVA/I) and to evaluate their physicochemical properties, antimicrobial activity, and cytotoxicity. Methods: Hydrophilic ointment formulations containing 2.5%, 5.0%, and 10.0% D/PVA/I were prepared using a PEG-based matrix composed of PEG 4000, PEG 400, and glycerol. Physicochemical characterization included organoleptic evaluation, pH measurement, rheological analysis, and UV–visible (Ultraviolet–visible) spectroscopy. Antimicrobial activity was assessed using agar diffusion and minimum bactericidal concentration (MBC) assays against Staphylococcus aureus, Escherichia coli, Enterococcus hirae, and Pseudomonas aeruginosa. Cytotoxicity was evaluated in Madin–Darby Canine Kidney (MDCK) cells using the MTT assay. Results: All formulations exhibited homogeneous semisolid structure and physiologically acceptable pH values (4.94–5.45). Rheological analysis demonstrated non-Newtonian pseudoplastic (shear-thinning) behavior. The flow behavior index (n) ranged from 0.03 to 0.33 according to the Ostwald–de Waele model, confirming shear-thinning characteristics, while viscosity increased with increasing D/PVA/I concentration. UV–visible spectroscopy confirmed the presence of triiodide ions (I_3⁻), characterized by absorption maxima at approximately 287 and 350 nm, indicating preservation of active iodine species within the PEG matrix, while placebo (blank) formulation analysis confirmed the absence of corresponding absorption bands, demonstrating that the PEG-based matrix does not contribute to the characteristic spectral features. The formulations demonstrated broad-spectrum antimicrobial activity, with MBC values ranging from 0.01 to 0.02 µg/mL. Cytotoxicity studies revealed moderate toxicity of the D/PVA/I complex (CC₅₀ = 0.82%) (50% cytotoxic concentration (CC₅₀) and significantly lower toxicity of the PEG-based ointment base (CC₅₀ = 18.38%). Conclusions: The developed PEG-based hydrophilic ointment formulations containing the D/PVA/I complex demonstrated favorable physicochemical characteristics, stability of iodine species, pronounced antimicrobial activity, and acceptable cytotoxicity profiles. These findings highlight the potential for the developed systems to be promising topical antimicrobial formulations.

Introduction.The growth of antibiotic resistance poses a threat to the global health system and is increasing interest in antimicrobial potentiators. Iodine-based compounds are characterized by low resistance to bacteria and a broad spectrum of action. For their use at the industrial level, it is important to scale up the technology and obtain a stable quality product. Research objective. To conduct the process of scaling up an iodine-based antimicrobial pharmaceutical substance in pilot production conditions, optimize technological parameters and evaluate the quality and stability characteristics of the finished product. Research materials and methods. The study was conducted in the pilot production and laboratories of the JSC « Scientific Center for Anti-Infective Drugs». A substance containing iodine, potassium iodide, starch, polyvinyl alcohol and neutral salts was prepared. Physicochemical analyses (pH, density, quantitative composition), microbiological purity and 12-month stability tests were conducted. Three production batches were prepared and the data were processed. Results. The quality of the finished product met all regulatory requirements: iodine content 8.33–8.39 mg/ml, potassium iodide – 11.73-11.83 mg/ml, pH – 4.24-4.27, density – 1.062-1.063. Microbiological purity indicators fully comply with the requirements. During the study, important technological parameters were analyzed at the main stages of production (raw material measurement, mixing, hydrolysis, obtaining the finished product, quality control, packaging and labeling). Conclusion. The results obtained during the scaling-up of an iodine-based antimicrobial substance are an important scientific and technological base that will allow this substance to be introduced into industrial production. The scaled-up technology allows for the production of high-quality, stable and safe products. As a result of scaling up from the laboratory level to the pilot production site, the critical parameters for the production of an iodine-based antimicrobial potentiator were identified and the technological conditions were optimized. The results obtained will serve as the basis for introducing the pharmaceutical substance into industrial production and will contribute to meeting its growing demand.